title: Clonal origin of Epstein-Barr virus (EBV)-infected T/NK-cell subpopulations in EBV-positive T/NK-cell lymphoproliferative disorders of childhood.
abstract: BACKGROUND
  In Japan, chronic active Epstein-Barr virus infection (CAEBV) may manifest with infection of T-cells or NK-cells, clonal lymphoid proliferations, and overt lymphoid malignancy. These EBV-positive lymphoproliferative disorders (EBV(+)LPD) of childhood are related to, but distinct from the infectious mononucleosis-like CAEBV seen in Western populations. The clonal nature of viral infection within lymphoid subsets of patients with EBV(+)LPD of childhood is not well described.
  
  
  OBJECTIVE
  Viral distribution and clonotype were assessed within T-cell subsets, NK-cells, and CD34(+)stem cells following high purity cell sorting.
  
  
  METHODS
  Six Japanese patients with EBV(+)LPD of childhood (3 T-cell LPD and 3 NK-cell LPD) were recruited. Prior to immunochemotherapy, viral loads and clonal analyses of T-cell subsets, NK-cells, and CD34(+)stem cells were studied by high-accuracy cell sorting (>99.5%), Southern blotting and real-time polymerase chain reaction.
  
  
  RESULTS
  Patient 1 had a monoclonal proliferation of EBV-infected γδT-cells and carried a lower copy number of EBV in αβT-cells. Patients 2 and 3 had clonal expansions of EBV-infected CD4(+)T-cells, and lower EBV load in NK-cells. Patients 4, 5 and 6 had EBV(+)NK-cell expansions with higher EBV load than T-cells. EBV-terminal repeats were determined as clonal bands in the minor targeted populations of 5 patients. The size of terminal repeats indicated the same clonotype in minor subsets as in the major subsets of four patients. EBV was not, however, detected in the bone marrow-derived CD34(+)stem cells of patients.
  
  
  CONCLUSIONS
  A single EBV clonotype may infect multiple NK-cell and T-cell subsets of patients with EBV(+)LPD of childhood. CD34(+)stem cells are spared, suggesting infection of more differentiated elements.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. ohgas@pediatr.med.kyushu-u.ac.jp
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Masataka
authors.initials: M
authors.lastname: Ishimura
authors.forename: Goichi
authors.initials: G
authors.lastname: Yoshimoto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takada
authors.forename: Tamami
authors.initials: T
authors.lastname: Tanaka
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Imadome
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Abe
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D015139:Blotting, Southern / Q000379:methods; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D007564:Japan; D007694:Killer Cells, Natural / Q000473:pathology / Q000821:virology*; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000473:pathology / Q000821:virology; D013601:T-Lymphocytes / Q000473:pathology / Q000821:virology*; D019562:Viral Load
chemical_list: D018952:Antigens, CD34; D004279:DNA, Viral